Cancer and Alzheimer's disease are major threats to the public health. While both diseases are still being understood, epidemiological and clinical studies suggest that there is an inverse association between cancer and Alzheimer's disease. The intriguing inverse association has stimulated the hope that the understanding of the mechanisms underlying the inverse association may lead to novel therapies for both diseases. Several plausible biological mechanisms have been postulated. For example, several groups have suggested that cancer and Alzheimer's disease may share same genes (e.g., TP53 and PIN1) and biological pathways (e.g., Wnt) related to activation and deregulation of the cell cycle. While the genetic links between cancer and Alzheimer's disease are biological plausibility that contributes to the observed inverse comorbidity, the complexity of the two groups of diseases obviously is beyond genetic definition, suggesting that other processes and mechanisms deserve serious consideration and rigorous examination.
In fact, after long debates about the causative agents of Alzheimer's disease, now it is suggested that amyloid oligomers are the most neurotoxic species. Recent studies also suggest that the early aggregates of misfolded non-disease-associated proteins and oligomers of disease-associated proteins (e.g., Aβs) exhibit similar inherent cytotoxicity, an important mechanistic advance that implies a common mechanism of the cytotoxicity of the aggregates. Since the aggregation of proteins (especially aberrant proteins), which represents a kinetically trapped state, is not directly defined at the genetic level, the elucidation of the molecular mechanism of the cytotoxicity of the aggregates may provide new information that eludes genetic studies. Despite its potential significance, the common origin of the cytotoxicity of the aggregates of aberrant proteins remains to be established.